Increased protein glycation in people with diabetes may promote atherosclerosis. This study examined the effects of non-enzymatic glycation on the association of lipid-free apolipoproteinA-I (apoA-I) with phospholipid, and cholesterol efflux from lipid-loaded macrophages to lipid-free and lipid-associated apoA-I. Glycation of lipid-free apoA-I by methylglyoxal and glycolaldehyde resulted in Arg...

OBJECTIVE The objective of this study was to determine the effects and potential mechanisms of C-reactive protein (CRP) on cholesterol efflux from human macrophage foam cells, which may play a critical role in atherogenesis. METHODS AND RESULTS Human THP-1 monocytes and peripheral blood mononuclear cells (PBMCs) were preincubated with acetylated LDL and [3H]-cholesterol to form foam cells, wh...

Cholesterol efflux from human monocyte-derived macrophages in the absence of exogenous acceptors has been described, but is unclear in mechanism. We investigated this process in relation to the expression of relevant genes, intracellular cholesterol storage and apoE secretion using drugs affecting different aspects of cholesterol metabolism. Both natural (22R-hydroxycholesterol/9-cis-retinoic a...

Clinical trials suggest that fenofibrate reduces the progression of retinopathies in patients with type 2 diabetes. Furthermore, patients with retinopathies have elevated levels of inflammatory chemokines and dysfunctional retinal angiogenesis. Therefore, we investigated the effects of fenofibrate on the production of inflammatory chemokines and genes associated with angiogenesis. Retinal pigme...

The concept that macrophages can become foam cells as a result of a disturbed balance between the uptake of cholesterol from lipoproteins and cholesterol efflux is generally accepted. ABCA1 and ABCG1 are two cholesterol transporters that may act sequentially to remove cellular cholesterol, but currently their combined role in vivo is unknown. We report here that targeted disruption of both ABCA...

Reverse cholesterol transport (RCT) is a mechanism critical to the anti-atherogenic property of HDL. Although citrulline contributes to the amelioration of atherosclerosis via endothelial nitric oxide production, it remains unclear whether it affects RCT. This study was undertaken to clarify the effects of citrulline on expressions of specific transporters such as ATP binding cassette transport...

Inhibitory effect of ark shell (Scapharca subcrenata (Lischke, 1869)) proteolytic hydrolysates (ASHs) on oxidized low-density lipoprotein (oxLDL)-induced macrophage foam cell formation was investigated. Two types ASHs were prepared by Alcalase® and pepsin, ASAH (ark shell-Alcalase® hydrolysates), ASPH shell-pepsin hydrolysate). Oil Red O staining results showed that suppressed lipid accumulatio...

Leukocytosis is associated with increased cardiovascular disease risk in humans and develops in hypercholesterolemic atherosclerotic animal models. Leukocytosis is associated with the proliferation of hematopoietic stem and multipotential progenitor cells (HSPCs) in mice with deficiencies of the cholesterol efflux-promoting ABC transporters ABCA1 and ABCG1 in BM cells. Here, we have determined ...

BACKGROUND The nuclear receptor liver X receptor (LXR) has two isoforms: LXRα and LXRβ. LXR activation promotes cholesterol efflux in macrophages, but the relative importance of each LXR isoform in mediating cholesterol efflux remains elusive. METHODS We evaluated the ability of different doses of LXRs agonist T0901317 to affect cholesterol efflux in human macrophages and its relationship wit...

RATIONALE High-density lipoprotein (HDL) is a heterogeneous population of particles. Differences in the capacities of HDL subfractions to remove cellular cholesterol may explain variable correlations between HDL-cholesterol and cardiovascular risk and inform future targets for HDL-related therapies. The ATP binding cassette transporter A1 (ABCA1) facilitates cholesterol efflux to lipid-free apo...